中药药理与临床2025,Vol.41Issue(7):57-62,6.
熊胆粉抑制神经炎症改善小鼠实验性自身免疫性脑脊髓炎作用及机制研究
Effect and Mechanism of Bear Bile Powder on Improving Experimental Autoimmune Encephalomyelitis in Mice via Inhibition of Neuroinflammation
摘要
Abstract
Objective:This paper investigated the inhibitory effect of bear bile powder on experimental autoimmune encephalomyelitis(EAE)in mice and explored its mechanism of action from the perspectives of attenuating neuroinflammatory response and improving nerve damage and myelin deficiency.Methods:C57BL/6 female mice were randomly divided into the normal control group,the model control group,0.1 g/kg and 0.05 g/kg bear bile powder groups,and 0.02 g/kg methylprednisolone group.The classical multiple sclerosis(MS)animal model was established,namely EAE model.2 d before modeling,mice in the bear bile powder groups were administered with drugs continuously for 23 d,while mice in 0.02 g/kg methylprednisolone group were administered intraperitoneally for three days from the 13th day of modeling.Af-ter EAE induction,neurobehavioral changes of mice were scored daily,and neurological function was evaluated.Tissues were sampled at the end of the drug administration,and histopathological changes in the spinal cord of mice were detected by HE and LFB staining.The activation of astrocytes and microglia in the cerebral cortex of mice was detected by immunofluorescence staining.The mRNA expression of inflamma-tion-related genes was detected by RT-qPCR.The expressions of inflammation-related proteins and NF-κB signaling pathway-related proteins were detected by Western blot.Results:Compared with the normal control group,mice in the model control group showed higher neurobehav-ioral scores and severe morbidity(P<0.01).A large number of inflammatory infiltration was observed in the white matter region of the mouse spinal cord,and a severe degree of demyelination was shown(P<0.01).The fluorescence intensity of GFAP and Iba-1 was enhanced in the cerebral cortical tissue of the mice,and the number of activated astrocytes was significantly increased(P<0.01).The expression levels of in-flammatory genes of iNos,Cox2,Il1β,Il6,and Tnfɑ were significantly increased(P<0.01 or P<0.01),and the protein expression levels of iN-OS,GFAP,Iba-1,p-NFκB,p-IκBα,and p-AKT were significantly up-regulated(P<0.05 or P<0.01).Compared with the model control group,the bear bile powder had significantly low neurobehavioral scores,and the degree of neurological impairment was improved in mice(P<0.01).Fewer areas of inflammatory infiltration were observed in mouse spinal cord tissue,and the degree of demyelination was significantly improved(P<0.01).Moreover,the fluorescence intensities of GFAP and Iba-1 were weakened in the cerebral cortex tissues of mice,and the activation of astrocytes was significantly inhibited(P<0.01).The gene expression levels of iNos,Cox2,Il1β,Il6,and Tnfɑ were significantly down-regulated(P<0.05 or P<0.01),while the protein expression levels of iNOS,GFAP,Iba-1,p-NFκB,p-IκBα,and p-AKT were signifi-cantly down-regulated(P<0.05 or P<0.01).Conclusion:Bear bile powder may exert its therapeutic effect on EAE by inhibiting the activa-tion of the AKT/NFκB signaling pathway and reducing the neuroinflammation caused by astrocyte and microglia activation.关键词
熊胆粉/实验性自身免疫性脑脊髓炎/多发性硬化/神经炎症/胶质细胞/核因子κBKey words
Bear bile powder/Experimental autoimmune encephalomyelitis/Multiple sclerosis/Neuroinflammation/Glial cell/NF-κB引用本文复制引用
王梦雪,吴晓俊,白语嫣,韩欣妍,倪晨阳,杨柳,袁金凤,吴辉,黄菲,石海莲..熊胆粉抑制神经炎症改善小鼠实验性自身免疫性脑脊髓炎作用及机制研究[J].中药药理与临床,2025,41(7):57-62,6.基金项目
国家自然科学基金(编号:82074043、82374065). (编号:82074043、82374065)